Diseases that afflict the brain are associated with high morbidity for patients and their families and incur a tremendous burden to individuals and to society. Understanding the brain's capacity for plasticity is an important step in the effort to design treatments aimed at enhancing the ability of the nervous system to recover after injury. Hence it is essential to study in detail how the adult brain adjusts after injury and the conditions that promote adaptive reorganization. Visual malfunction is a common corollary of cortical injury. Area V1 provides the chief relay of visual information to extrastriate visual areas, so it is not surprising that primary visual cortical injuries produce a dense visual field scotoma. Nevertheless, a series of studies performed over the last 25 years has provided strong evidence that primate (human and monkey) subjects still possess significant residual visual capacity in the blind part of their visual field following complete area V1 lesions (see Weiskrantz, Prog. Brain Res. 144:229-41, 2004 for a review). This phenomenon has been dubbed "blindsight" reflecting the fact that the visual perceptual capacity remaining following V1 lesions is weak, requires specific conditions to be manifested, and is often associated with absence of visual awareness. These constraints make it essentially impossible for patients to use this capacity for practical benefit. "Blindsight" is likely mediated by one of several pathways that can convey information to extrastriate cortex by bypassing area V1, but areas involved have not been conclusively deciphered. Area V2, because of its status as the next cortical relay of visual information following V1, is an attractive candidate for mediating "blindsight", as well as an attractive target for manipulations designed to restore or strengthen visually driven behavior following V1 lesions. Human functional magnetic resonance imaging (fMRI) studies recently demonstrated V2 activity several years following area V1 lesions (Baseler et al., J Neurosci 19(7):2619-27,1999;Schoenfeld et al. Ann Neurol 52(6):814-24, 2002). This agrees with our own preliminary fMRI data in a macaque model of isolated V1 injury, which show significant visually driven activation inside the deafferented portion of area V2 by one month following a chronic V1 lesion (Schmid et al., Soc. Neurosci. Abs. 122.2, 2007). Unfortunately, this degree of area V2 reactivation is evidently not sufficient to reconstitute high levels of visual performance. Here we propose to use macaque fMRI and electrophysiology to: i) study the topography and the mechanism of area V2 reorganization after V1 lesions in the presence and absence of training, ii) correlate the strength of V2 reorganization to behavioral recovery in a relevant contrast detection task, and iii) permanently improve behavioral performance by pairing visual stimulation with intracortical microstimulation during training to promote area V2 reorganization. To date no reliable method exists for successfully rehabilitating subjects with lesions of the primary visual cortex who experience a profound loss of visual perception in the affected portion of the visual field. Our experiments will explore the potential of area V2 as a target for future intervention, and will specifically test intracortical microstimulation for improving behavioral ("blindsight") performance. The macaque model of cortical reorganization studied with the combination of electrophysiology methods and fMRI is a versatile and sensitive tool for testing experimental hypotheses on the nature of plasticity. PUBLIC HEALTH RELEVANCE: To date no reliable method exists to rehabilitate effectively subjects with lesions of the primary visual cortex who experience a profound loss of visual perception in the affected portion of the visual field. Our experiments couple state of the art functional magnetic resonance imaging and electrophysiology methods to study the degree of cortical reorganization in area V2 following primary visual cortical injury and how it relates to improved behavioral performance in a relevant visual task. In addition, we will focus on investigating the potential of area V2 as a target for future intervention, and will specifically test the capacity of one such promising intervention (microstimulation) for improving performance.